HMGB1-induced autophagy promotes chemotherapy resistance in leukemia cells

Liu, L; Yang, Minghua; Kang, Rui; Wang, Z; Zhao, Ying; Yu, Yan; Xie, Min; Yin, Xiao-Cheng; Livesey, Kristen M.; Lotze, Michael T.; Tang, Daolin; Cao, Lizhi

doi:10.1038/leu.2010.225

Cited by 215 publications

(209 citation statements)

References 47 publications

(60 reference statements)

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“…The prototypical damage-associated molecular pattern molecule (DAMP) (45), HMGB1 is released with sustained autophagy (22,23,40,41,47), late apoptosis (1), and necrosis (34). Consistently, HMGB1 was released by pancreatic cancer cells (Panc2.03, Panc02, and Panc1.28) during oxidative injury (Fig.…”

Section: Upregulation Of Rage Expression In H 2 O 2 -Induced Oxidativsupporting

confidence: 51%

The Receptor for Advanced Glycation End-Products (RAGE) Protects Pancreatic Tumor Cells Against Oxidative Injury

Kang

Tang

Livesey

et al. 2011

Antioxidants & Redox Signaling

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Reactive oxygen species, including hydrogen peroxide (H 2 O 2 ), can cause toxicity and act as signaling molecules in various pathways regulating both cell survival and cell death. However, the sequence of events between the oxidative insult and cell damage remains unclear. In the current study, we investigated the effect of oxidative stress on activation of the Receptor for Advanced Glycation End-products (RAGE) and subsequent protection against H 2 O 2 -induced pancreatic tumor cell damage. We found that exposure of pancreatic tumor cells to H 2 O 2 provoked a nuclear factor kappa B (NF-kB)-dependent increase in RAGE expression. Further, suppression of RAGE expression by RNA interference increased the sensitivity of pancreatic tumor cells to oxidative injury. Furthermore, targeted knockdown of RAGE led to increased cell death by apoptosis and diminished cell survival by autophagy during H 2 O 2 -induced oxidative injury. Moreover, we demonstrate that RAGE is a positive feedback regulator for NF-kB as knockdown of RAGE decreased H 2 O 2 -induced activity of NF-kB. Taken together, these results suggest that RAGE is an important regulator of oxidative injury. Antioxid. Redox Signal. 15, 2175-2184.

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Section: Upregulation Of Rage Expression In H 2 O 2 -Induced Oxidativsupporting

confidence: 51%

The Receptor for Advanced Glycation End-Products (RAGE) Protects Pancreatic Tumor Cells Against Oxidative Injury

Kang

Tang

Livesey

et al. 2011

Antioxidants & Redox Signaling

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“…[50][51][52][53] Delivery of exogenous HMGB1 protein to cells triggers autophagy or apoptosis in cancer cells, depending on its redox status and receptors. Reducible HMGB1 (i.e., where the cysteines are not terminally oxidized) binds to the receptor for advanced glycation end products (RAGE), induces Beclin 1-dependent autophagy, and promotes pancreatic or colon tumor cell line resistance to chemotherapeutic agents and ionizing radiation.…”

Section: Other Beclin 1-binding Proteins In Autophagymentioning

confidence: 99%

The Beclin 1 network regulates autophagy and apoptosis

et al. 2011

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Beclin 1, the mammalian orthologue of yeast Atg6, has a central role in autophagy, a process of programmed cell survival, which is increased during periods of cell stress and extinguished during the cell cycle. It interacts with several cofactors (Atg14L, UVRAG, Bif-1, Rubicon, Ambra1, HMGB1, nPIST, VMP1, SLAM, IP 3 R, PINK and survivin) to regulate the lipid kinase Vps-34 protein and promote formation of Beclin 1-Vps34-Vps15 core complexes, thereby inducing autophagy. In contrast, the BH3 domain of Beclin 1 is bound to, and inhibited by Bcl-2 or Bcl-XL. This interaction can be disrupted by phosphorylation of Bcl-2 and Beclin 1, or ubiquitination of Beclin 1. Interestingly, caspase-mediated cleavage of Beclin 1 promotes crosstalk between apoptosis and autophagy. Beclin 1 dysfunction has been implicated in many disorders, including cancer and neurodegeneration. Here, we summarize new findings regarding the organization and function of the Beclin 1 network in cellular homeostasis, focusing on the cross-regulation between apoptosis and autophagy. Cell Death and Differentiation (2011) 18, 571-580; doi:10.1038/cdd.2010 published online 11 February 2011 Autophagy is an essential process that consists of selective degradation of cellular components. There are at least three different types of autophagy described and possibly more. These autophagy types include macroautophagy (hereafter referred to as autophagy), microautophagy and chaperonemediated autophagy. 1 The initial step of autophagy is the surrounding and sequestering of cytoplasmic organelles and proteins within an isolation membrane (phagophore). Potential sources for the membrane to generate the phagophore include the Golgi complex, endosomes, the endoplasmic reticulum (ER), mitochondria and the plasma membrane. 2 The nascent membranes are fused at their edges to form double-membrane vesicles, called autophagosomes. Autophagosomes undergo a stepwise maturation process, including fusion with acidified endosomal and/or lysosomal vesicles, eventually leading to the delivery of cytoplasmic contents to lysosomal components, where they fuse, then degrade and are recycled (Figure 1a). The process of mammalian autophagy is divided into six principal steps: initiation (Figure 1b It has been well demonstrated that autophagy depends on Atg5/Atg7, is associated with microtubule-associated protein light chain 3 (LC3) truncation and lipidation, and may originate directly from the ER membrane and other membrane organelles. Furthermore, recent study has identified a Atg5/Atg7-independent pathway of autophagy. 3 This pathway of autophagy was not associated with LC3 processing but appeared to involve autophagosome formation from late endosomes and the trans-Golgi. 3 Atg7-independent autophagy had been implicated in mitochondrial clearance from reticulocytes. 4 The exact molecular basis of Atg5/Atg7-independent autophagy remains to be elucidated. Interestingly, Beclin 1 is required for Atg5/Atg7-dependent and -independent autophagy. 3 However, the presence of Beclin 1-indep...

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“…CML cells expressing BCR/ABL oncoprotein at high levels were shown to induce autophagy in order to recover from targeted and nontargeted treatment options, indicating the protective effect of autophagy in CML [109]. These findings are supported by another recent report that indicated that the release of specific damage-associated molecular pattern molecules (DAMPs) after chemotherapy conferred drug resistance to leukemic cells by activating the autophagic pathway [110,111]. In addition to these findings, B-cell CLL was also shown to develop resistance to the tyrosine kinase inhibitor dasatinib by activating autophagy [112] In another report, overexpression of the melanoma differentiation-associated gene-7/interleukin-24 (mda-7/IL-24) was shown to induce autophagy and confer survival advantage to leukemic cells [113].…”

Section: Importance Of Autophagy In Leukemic Cell Survival and Drug Rmentioning

confidence: 56%

Role of autophagy in the progression and suppression of leukemias

Ekiz

Can

Baran

2012

Critical Reviews in Oncology/Hematology

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Autophagy is a physiological process in which cellular components are degraded by the lysosomal machinery. Thereby, organelles are recycled and monomers are produced in order to maintain energy production. Current studies indicate autophagy might suppress or augment survival of cancer cells. Therefore, by elucidating the role of autophagy in cancer pathogenesis, novel therapeutic intervention points may be revealed. Leukemia therapy has advanced in recent years; but a definitive cure is still lacking. Since autophagy often is deregulated in this particular type of cancer, it is clear that future findings will have clinical implications. This review will discuss the current knowledge of autophagy in blood cancers. © 2011 Elsevier Ireland Ltd

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HMGB1-induced autophagy promotes chemotherapy resistance in leukemia cells

Cited by 215 publications

References 47 publications

The Receptor for Advanced Glycation End-Products (RAGE) Protects Pancreatic Tumor Cells Against Oxidative Injury

The Receptor for Advanced Glycation End-Products (RAGE) Protects Pancreatic Tumor Cells Against Oxidative Injury

The Beclin 1 network regulates autophagy and apoptosis

Role of autophagy in the progression and suppression of leukemias

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